Analyses of human effector T cell repertoire in renal allograft rejection indicate that responses to a particular alloantigen, or a number of alloantigens, do not utilize all the available repertoire, but that some T cells have a selective advantage giving rise to predominant clonotypes. The advantage appears to be a result of an expression of a particular T cell antigen receptor beta chain gene. Using T cell lines established from lymphocytes infiltrating a rejected allograft, we propose to clone and sequence the predominant TcR beta chain gene to understand the molecular basis for their selection. The long term goals of this project are to use this knowledge to design ways of specifically eliminating or down-regulating the selected clonotypes in order to achieve prolonged graft survival. The immediate benefit of this project will be a greater understanding of the relationship between the structure of the T cell antigen receptor and its function in the recognition of antigen/MHC or foreign antigen alone.